Synthesis and Antiviral Activity of 21β-Acetyl-20β,28-Epoxy-18α,19βH-Ursane Derivatives Against Influenza H1N1 and SARS-Cov-2 Spike Pseudovirus

Synthesis and Antiviral Activity of 21β-Acetyl-20β,28-Epoxy-18α,19βH-Ursane Derivatives Against Influenza H1N1 and SARS-Cov-2 Spike Pseudovirus Full article

Journal

Chemistry of Natural Compounds
ISSN: 0009-3130 , E-ISSN: 1573-8388

Output data

Year: 2024, Volume: 60, Number: 2, Pages: 275-282 Pages count : 8 DOI: 10.1007/s10600-024-04302-w

Tags

pentacyclic triterpenoids allobetulin ursane antiviral activity influenza A SARS-CoV-2

Authors

Khusnutdinova E.F. ¹ , Galimova Z.I. ¹ , Petrova A.V. ¹ , Tretyakova E.V. ¹ , Smirnova I.E. ¹ , Slita A.V. ² , Fedij S.V. ³ , Zarubaev V.V. ² , Xiao S. ⁴ , Ma X. ⁴ , Zhou D. ^4,5 , Rybalova T.V. ⁶ , Polovyanenko D.N. ⁶ , Kazakova O.B. ¹

Affiliations

1	Ufa Institute of Chemistry UFRC RAS
2	Department of Virology, Experimental Virology Laboratory, St. Petersburg Pasteur Institute of Epidemiology and Microbiology
3	St. Petersburg State University
4	State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University
5	Institute of Chemical Biology, Shenzhen Bay Laboratory
6	N. N. Vorozhtzov Novosibirsk Institute of Organic Chemistry SB RAS

Allobetulin derivatives with rearranged E-ring exhibit important pharmacological properties against various viral pathogens. Basing on 3β-acetoxy-21β-acetyl-20β,28-epoxy-18α,19βH-ursane triterpenoid, obtained from allobetulin in one stage, a series of new derivatives have been synthesized and their antiviral activity against both influenza virus A (H1N1) and SARS-CoV-2 pseudovirus was evaluated. Among them, 2,3-indolo-allobetulone N-propargyl derivatives were the most efficacious against influenza virus with low toxicity (CC50 × 300 μM) and IC50 values of 7.04 to 3.5 μM and high selectivity indexes (SI 43 and 86). Compared with amodiaquine, a derivative with 3-pyridinylidene fragment 12 showed a weak antiviral activity against SARS-CoV-2 pseudovirus with an inhibition rate of 57.3% at a concentration of 20 μM. Further optimization to increase the cellular antiviral activity seems to be necessary to develop this series of triterpenoids as antiviral agents.

Khusnutdinova E.F. , Galimova Z.I. , Petrova A.V. , Tretyakova E.V. , Smirnova I.E. , Slita A.V. , Fedij S.V. , Zarubaev V.V. , Xiao S. , Ma X. , Zhou D. , Rybalova T.V. , Polovyanenko D.N. , Kazakova O.B.
Synthesis and Antiviral Activity of 21β-Acetyl-20β,28-Epoxy-18α,19βH-Ursane Derivatives Against Influenza H1N1 and SARS-Cov-2 Spike Pseudovirus
Chemistry of Natural Compounds. 2024. V.60. N2. P.275-282. DOI: 10.1007/s10600-024-04302-w

Submitted:	Jun 7, 2023
Published online:	Mar 26, 2024

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